Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies

Alzheimers Dement. 2017 Nov;13(11):1237-1250. doi: 10.1016/j.jalz.2017.03.001. Epub 2017 Apr 18.


Introduction: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB).

Methods: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time polymerase chain reaction (PCR) to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants.

Results: We identified four miRNA binding sites and observed a neuronal-type-specific expression profile for each miRNA in the different isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons. Furthermore, we found that the short structural variant rs777296100-polyT was moderately associated with DLB but not with PD.

Discussion: We suggest that the regulation of SNCA expression through miRNAs is neuronal-type-specific and possibly plays a part in the phenotypic heterogeneity of synucleinopathies. Furthermore, genetic variability in the SNCA gene may contribute to synucleinopathies in a pathology-specific manner.

Keywords: DLB; PD; SNCA; SNCA 3′ UTR; iPSC-derived neurons; miRNA.

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Aged
  • Aged, 80 and over
  • Binding Sites / genetics
  • Cells, Cultured
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Humans
  • Lewy Body Disease / genetics*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / metabolism
  • Stem Cells / drug effects
  • Stem Cells / physiology
  • alpha-Synuclein / genetics*


  • 3' Untranslated Regions
  • MicroRNAs
  • Nerve Tissue Proteins
  • RNA, Messenger
  • alpha-Synuclein